Reproductive toxicity of low level bisphenol A exposures in a two-generation zebrafish assay: Evidence of male-specific effects

• Published in: Aquatic toxicology Vol. 169; pp. 204 - 214
• Main Authors: Chen, Jiangfei, Xiao, Yanyan, Gai, Zengxin, Li, Rong, Zhu, Zixu, Bai, Chenglian, Tanguay, Robert L., Xu, Xiaojiang, Huang, Changjiang, Dong, Qiaoxiang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2015
• Subjects: Animals; Benzhydryl Compounds - toxicity; BPA; Chronic exposure; Danio rerio; Female; Freshwater; Gene Expression Regulation, Enzymologic - drug effects; Gonads - drug effects; Male; Methyltransferases - genetics; Mitochondrial biogenesis; Phenols - toxicity; Reproduction - drug effects; Sex Factors; Sex Ratio; Sperm; Water Pollutants, Chemical - toxicity; Wnt signaling; Zebrafish; Zebrafish - physiology; Zebrafish; BPA; Wnt signaling; Mitochondrial biogenesis; Sperm; Chronic exposure
• ISSN: 0166-445X; 1879-1514; 1879-1514
• DOI: 10.1016/j.aquatox.2015.10.020

•We used the zebrafish model to assess reproductive toxicity of chronic low level BPA exposure.•BPA exposure resulted in female-biased sex ratio, decreased sperm count/quality in F1/F2 adults.•BPA exposure led to paternal-mediated increase of malformation and mortality in F2 offspring.•BPA exposure disrupted mitochondrial biogenesis and Wnt signaling pathway in F2 male gonads.•BPA exposure reduced the expression of DNA methyltransferases in F2 offspring. Bisphenol A (BPA), a high-volume chemical used to make polycarbonate plastic and epoxy resins, is a ubiquitous contaminant in environment and human body. To investigate the reproductive effects of long-term exposure to low concentrations of BPA, a two-generation study was conducted using the aquatic model species of zebrafish. Our findings revealed that exposure to 1nM (0.228μg/L) BPA for continuous two generations resulted in female-biased sex ratio in both F1 and F2 adult population, decreased sperm density, and decreased sperm quality as measured by motility, velocity, ATP content and lipid peroxidation in F1 and F2 males. Females were less sensitive to BPA exposures than males as no adverse effects were found in female gonads or gametes. Delayed hatching at 48hpf and increased malformation and mortality were found in the offspring from BPA exposed F2, but not F1 parents. Most importantly, the adverse effect on larval development and survival from BPA exposed F2 parents was paternal-specific, resulting mainly from BPA exposed males. Subsequent transcription analysis of F2 male gonads revealed dysregulated mitochondrial biogenesis and significant activation of non-canonical Wnt/planar cell polarity and Wnt/Calcium signaling pathways. Gene expression analysis of larvae from BPA exposed F2 parents showed significant reduced expression of DNA methyltransferases such as dnmt1, dnmt3, and dnmt5. In conclusion, low level BPA exposures for continuous two generations not only affects sex ratio and sperm quantity/quality in F1 and F2 adults, reproductive success in offspring from F2 parents, but also perturbs various molecular pathways potentially contributing to these BPA induced male-specific reproductive defects.